1. Field of the Invention
The present invention relates generally to the fields of osteoclasts and bone. The invention provides surprisingly effective methods for inhibiting osteoclasts, reducing bone loss and treating conditions such as periodontitis and osteoporosis by administering a phenothiazine enantiomer, preferably the (+) enantiomer of promethazine, and associated medicaments, compositions and kits.
2. Description of Related Art
The two major cell types that form and degrade bone are the osteoblast and the osteoclast, respectively. The improper functioning of such cells can produce aberrant bone metabolism, which is linked to the development of several human diseases and disorders, e.g., periodontitis and osteoporosis.
Osteoporosis is defined as compromised bone strength that leads to an increased risk of fracture. This condition results from the mis-regulation of the osteoblast and the osteoclast, thus disturbing the balance of bone formation and degradation.
Osteoporosis is a significant problem in the elderly, in individuals with genetic defects and in those who undergo prolonged space flight. In the weightless environment, bone loss occurs at approximately 2% per month, due to decreased osteoblast activity without alteration in osteoclast activity. Post-menopausal osteoporosis poses a considerable health problem. Significant bone loss in women occurs following estrogen removal, which is due to an increase in osteoclastic activity.
In the United States, osteoporosis is responsible for more than 1.5 million factures annually, including 300,000 hip fractures, 700,000 vertebral fractures, 250,000 wrist fractures and 300,000 fractures at other sites. The estimated national direct expenditure (hospitals and nursing homes) for osteoporotic and associated fractures was $17 billion in 2001, and the cost is rising.
Although there is no cure for osteoporosis, the following medications are approved by the FDA for postmenopausal women to prevent and/or treat osteoporosis: bisphosphonates, such as alendronate (brand name Fosamax®), risedronate (brand name Actonel®); calcitonin (brand name Miacalcin®); estrogen/hormone replacement therapy, including estrogens (brand names, such as Climara®, Estrace®, Estraderm®, Estratab®, Ogen®, Premarin® and others) and estrogens and progestins (brand names, such as Activella®, FemHrt®, Premphase®, Prempro® and others) and selective estrogen receptor modulators (SERMs), such as Raloxifene (brand name Evista®).
Unfortunately, all current treatment modalities suffer from certain drawbacks. For example, the available medications are all expensive and problematical to dose. Importantly, most of the current treatments have serious side effects that result in secondary problems. For example, estrogen treatment is associated with increased risk of cancers in females.
Accordingly, there remains in the art a need for improved methods for preventing or treating bone loss, particularly bone loss associated with osteoporosis. The development of methods to prevent or reduce bone loss with higher efficacy and lower risk of side effects is highly desirable, particularly if the methods could be developed at relatively low cost.